The objective of this project is to elucidate the source of excessive collagen fibrils in and around diabetic vascular basement membrane (BM) that becomes rather selectively detrimental to retinal tissues due to Muller cell degeneration. The following methods will be used: (a) Comparative ultrastructual and biochemical studies of pathognomonic vascular BM lesions in human diabetics and in experimentally induced (by both diabetogenic chemical agents and EMC (encephalo-myocarditis) virus) animal diabetes. Several young olive baboons will be subjected to this project to extend our working hypothesis. The preferential susceptibility of the retinal tissues to diabetic condition will hopefully be accounted for the vulnerability of Muller cells due to its unique vascular pathology of diabetic BM lesions. (b) Comparative ultrastructural and biochemical studies of some characteristic vascular lesions in the central nervous system. Search for the mechanisms of a marked prohibitive action of astroglia at the blood-brain barrier may provide valuable information for an understanding of the pathogenesis of diabetic retinopathy. (c) Comparative studies of retinal tissue culture explants of diabetic animals with age-matched controls in order to clarify the cause of diabetic neovascularization.